The invention relates to a method for adsorbing or removing antimicrobial agents, also referred to as "inhibitors" or "inhibitory agents", contained in a biological fluid such as, in particular, blood; it also relates to. an apparatus for carrying out this method.
In the description and in the claims, the terms "antimicrobial agents", "inhibitory agents" or "inhibitors" are used to denote any agent intended for preventing the proliferation of microbes or pathogenic microorganisms, such as, for example, antibiotics, antifungals, antivirals and antiseptics.
The term "biological fluid" is used to denote any fluid containing living matter, such as plasma, cerebrospinal fluid, urine, synovial fluid and, preferably, blood.
In the remainder of the description, the invention will be essentially illustrated by its preferred application to blood.
For numerous applications, it is well known to adsorb the antibiotics contained in blood, in particular for the purpose of removing them in order thereafter to analyze the blood which has been purged in this way.
The detection of pathogenic microorganisms in biological fluids must be performed in the shortest possible time, in particular in. the case of septicemia for which the mortality remains high in spite of the broad range of antibiotics which are available to doctors. In order to increase sick individuals' chances of survival, practitioners often administer an antibiotic or mixture of antibiotics to the patients. It is, however, important to determine a suitable antibiotic therapy as soon as possible. Unfortunately, the isolation and rapid characterization of infectious microorganisms is difficult when the blood samples to be analyzed contain inhibitory agents such as antibiotics, which often slow down or even abolish microbial growth.
The same applies to the microorganisms responsible for meningitis, whose presence in the cerebrospinal fluid must be detected with the utmost speed. Here too, the presence of antibiotics may interfere with this detection.
Bacteriuria may also be difficult to diagnose when the patient is subjected to antibiotic therapy and excretes antibiotics in the urine. Frequently, the isolation of infectious microorganisms can be negative.
In order to remedy these drawbacks and improve the detection of the microbes and their isolation in samples of biological fluids from patients on antibiotic therapy, several methods have already been proposed which are directed towards removing or neutralizing the antibodies present in the blood before analyzing the blood which has been purged in this way.
In the first place, the proposal has been made to pass the blood over ion exchange resins or adsorbent polymers. For this purpose, the blood drawn from the patient is placed in a first bottle containing such resins or such polymers, and the whole is gently agitated for a suitable time. A volume of this purged blood is then transferred to a second bottle containing the culture medium which is suitable for the growth of the microorganisms possibly present. This technique permits good adsorption of most antibiotics. However, since the adsorbent materials take the form of granules or powder included in the first bottles, this technique separate from the drawing of the blood itself necessitates an additional step of taking up and transfering the blood which has been purged in this way, which is expensive and sometimes of questionable efficiency inasmuch as not all the antibiotics present are adsorbed, and sometimes gives rise to releases with the passage of time.
The suggestion has also been made to employ resins contained directly in analysis bottles containing the culture medium. Here too, risks of release of the inhibitory agents with the passage of time and risks of inhibition due to the very composition of the resins are observed.
In the document EP-A-0,597,542 corresponding to the document U.S. Pat. No. 5,314,855, an adsorbent composition has been proposed consisting of a mixture of active charcoal, fuller's earth, a powdered anion exchange resin and a mixture of cationic and anionic polyelectrolytes. This technique has, however, the same drawbacks as those of ion exchange resins. In effect, in this method, the blood is first drawn and then, away from the place where it has been drawn, is simultaneously treated and analyzed in the analysis bottle containing a suitable culture broth and the adsorbent composition.
In addition, since the antibiotic remains in the mixture, as before, risks of release are observed. Moreover, the presence of active charcoal in suspension interferes with the analysis in the bottle, since this charcoal can adsorb other compounds, in particular factors needed for the growth of the microorganisms, thereby inducing false-negative results. In addition, the exchange surface areas often prove insufficient for adsorbing in their entirety the inhibitory agents present in the drawn sample, so that the filled bottle must be agitated significantly in order to obtain a good exchange efficiency. Lastly, as a result of the presence of active charcoal, this technique can make it difficult to carry out further examinations such as, in particular, direct reading by eye or under a microscope.